Impact of different classes antimicrobial agents on plasma endotoxin activity
D. Nitsche, C. Schulze, S. Oesser, A. Dalhoff and M. Sack
Surgical Research, University of Kiel, Germany.
OBJECTIVE: To investigate the influence of different classes and doses of
antibiotics on endotoxin release in gram-negative infection in a rat model
of intra- abdominal infection. DESIGN: Immediately after intraperitoneal
inoculation of Escherichia coli (5 x 10(7) colony-forming units/kg),
anesthetized Wistar rats were treated with a single intravenous dose of an
antimicrobial agent: cefotaxime (40 mg/kg), ciprofloxacin (3 mg/kg or 6
mg/kg), imipenem (7 mg/kg or 14 mg/kg), or gentamicin (5 mg/kg). An
untreated control group received 0.9% sodium chloride instead of
antibiotic. Plasma endotoxin activity, blood bacteria count, and mean
arterial pressure were monitored at 60-minute intervals for 5 hours. At the
end of the experiment, lavage was performed to determine the bacteria count
in the peritoneal cavity. RESULTS: In the untreated group, the blood
bacteria count increased rapidly. Five hours after therapy, the plasma
endotoxin activity in the cefotaxime group was higher by a factor of 3.6
than in the untreated group. Compared with the cefotaxime group, endotoxin
activity was approximately 26% lower in the ciprofloxacin (3 mg/kg) group,
35% lower in the imipenem groups, and 38% lower in the gentamicin group.
The lowest endotoxin levels were in the high-dose ciprofloxacin group.
Bacteria counts in the peritoneal cavity were lowest in the gentamicin and
high-dose ciprofloxacin groups. Except in the high-dose ciprofloxacin
group, the endotoxin increase in the therapy groups was associated with a
significant (P < .05) decrease in mean arterial pressure. CONCLUSIONS:
In the early phase of therapy, antibiotic-induced endotoxin release is
influenced by the mode of action of the agent class. This is not the sole
influence in every class. With quinolones, this effect is also influenced
considerably by dosage, ie, by pharmacodynamics.
